DESCRIPTION This research proposal represents an important part of the overall effort to understand protein aggregation associated diseases, including Alzheimer's, Huntington's and Parkinson's Diseases. Protein aggregates and abnormal tissue deposits of normally soluble proteins have been found in the patients suffering from these disease. It is important to understand the structure and function of these aggregates in order to devise methods for diagnosis and cures for these diseases. This proposal addresses studying the structure of amyloid fibrils, a type of aggregate, which is associated with Alzheimer's Disease. Analytical techniques including hydrogen deuterium exchange mass spectrometry and microscale separation techniques will be utilized to define the hydrogen bonding and extent of beta-sheet network in the amyloid fibrils present in Alzheimer's Disease.